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Integration of expression profiles and genetic mapping data to identify candidate genes in intracranial aneurysm

机译：表达谱和遗传图谱数据的整合，以鉴定颅内动脉瘤中的候选基因

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摘要

Intracranial aneurysm (IA) is a complex genetic disease for which, to date,10 loci have been identified by linkage. Identification of the riskconferring genes in the loci has proven difficult, since the regions often contain several hundreds of genes. An approach to prioritize positional candidate genes for further studies is to use gene expression data from diseased and nondiseased tissue. Genes that are not expressed, either in diseased or nondiseased tissue, are ranked as unlikely to contribute to the disease. We demonstrate an approach for integrating expression and genetic mapping data to identify likely pathways involved in the pathogenesis of a disease. We used expression profiles for IAs and nonaneurysmal intracranial arteries (IVs) together with the 10 reported linkage intervals for IA.Expressed genes were analyzed for membership in Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways. The 10 IA loci harbor 1,858 candidate genes, of which 1,561 (84%) were represented on the microarrays. We identified 810 positional candidate genes for IA that were expressed in IVs or IAs. Pathway information was available for 294 of these genes and involved 32 KEGG biological function pathways represented on at least 2 loci.A likelihood-based score was calculated to rank pathways for involvement in the pathogenesis of IA. Adherens junction, MAPK, and Notch signaling pathways ranked high. Integration of gene expression profiles with genetic mapping data for IA provides an approach to identify candidate genes that are more likely to function in the pathology of IA.
机译：颅内动脉瘤（IA）是一种复杂的遗传病，迄今为止，已通过连锁鉴定出了10个基因座。已经证明很难鉴定基因座中的风险赋予基因，因为该区域通常包含数百个基因。确定位置候选基因优先顺序以进行进一步研究的一种方法是使用来自患病和未患病组织的基因表达数据。在患病或未患病的组织中未表达的基因被列为不太可能导致该疾病。我们展示了一种整合表达和遗传作图数据以识别参与疾病发病机制的可能途径的方法。我们使用了IAs和非动脉瘤性颅内动脉（IVs）的表达谱以及10个报告的IA连锁间隔。分析了表达的基因在《京都基因与基因组百科全书》（KEGG）生物学途径中的成员资格。 10个IA位点包含1,858个候选基因，其中1,561个（84％）代表在微阵列上。我们确定了在IV或IAs中表达的810个IA的位置候选基因。现有294种基因的通路信息，涉及至少2个基因座上的32条KEGG生物学功能通路，并计算了基于似然度的评分来对参与IA发病机制的通路进行排序。粘附素连接，MAPK和Notch信号通路排名较高。基因表达谱与IA的遗传图谱数据的整合提供了一种方法来鉴定在IA病理中更可能发挥作用的候选基因。

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